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Research has indicated that maladaptive appraisals of cognitions and cognitive experiences (such as intrusive thoughts and auditory hallucinations) can maintain distress. Theories suggest this mechanism can explain why such experiences can fall on a continuum from unproblematic to distressing. This thesis focused on three involuntary cognitive experiences prevalent in nonclinical and clinical populations where this mechanism of distress has been hypothesised: tinnitus; obsessive intrusive thoughts (OITs); and involuntary musical imagery (INMI). Evaluation of the effectiveness of psychological interventions to reduce tinnitus distress, and investigation into appraisals of OITs and INMI and what might have influence over these was conducted. A systematic review and meta-analysis was conducted on 21 studies to identify and evaluate the effectiveness of psychological interventions for reducing tinnitus distress in adults. Large treatment effects emerged for cognitive-behavioural therapy (CBT) in both therapist-delivered and self-help formats. A very large treatment effect emerged for ‘other’ approaches including multidisciplinary combinations of sound therapy techniques with psychological intervention, mindfulness, and psychoeducation. It was concluded that cross-disciplinary combined interventions and those aimed at addressing maladaptive appraisals of tinnitus could facilitate a reduction in distress. Study limitations and clinical implications were discussed. The empirical chapter investigated OITs and INMI. Ninety-one UK university staff and students completed measures of OIT and INMI appraisal, perceived thought control and self-reported thought suppression. Additionally, the predictive influence of working memory on these measures was also explored. Participants completed a computerised operation span task to test working memory capacity (WMC). Significant relationships emerged between both negative OIT and INMI appraisal. Negative appraisal for both OITs and INMI were significantly associated with low perceived thought control, but this was weak for INMI. Negative OIT appraisal was significantly related to higher self-reported thought suppression. WMC did not significantly explain the variance in these variables. Study limitations and implications for clinical practice were discussed. In conclusion, the literature review highlighted effectiveness of interventions which challenge maladaptive appraisals in reducing tinnitus distress; and the empirical chapter drew associations between negative appraisals of involuntary cognitions, and beliefs about thought control. Together, the findings suggest commonalities in mechanisms of distress which may be extended across a range of experiences, including those traditionally considered to be unproblematic and which have only recently started to be explored (such as INMI). It is recommended that appraisals of other experiences which can cause distress, and potential interventions which target such appraisals, continue to be explored in future research.

Ubiquitination is a diverse post-translational modification, involved in a plethora of eukaryotic processes. At least three different enzymes are required for ubiquitination to occur: an ubiquitin-activating enzyme (E1), an ubiquitin-conjugating enzyme (E2) and an ubiquitin ligase (E3). Conversely, deubiquitinating enzymes (DUBs) regulate the removal of ubiquitin modifications. Together, this enzymatic machinery facilitates a wide array of ubiquitin modifications and further ubiquitin-like modifications. Such modifications play a significant role in the regulation of vital biological processes including proteasomal degradation, DNA damage response (DDR) and NF-κB signalling. Ubiquitination machinery can be studied using a chemical proteomics approach. Activity-based probes (ABPs) which covalently trap enzymes can be employed. Such probes possess bioorthogonal handles, which on ligation to complementary reporter groups enable enrichment of probe-enzyme complexes prior to LC-MS/MS, western blot, or fluorescent analysis. The design, synthesis, and development of six inhibitor-inspired ABPs for ubiquitin machinery is described. Both small molecule and peptide probes were explored, and assessed for their ability to act as ubiquitin machinery probes both in intact cells and cell lysate. Spike-in SILAC methodology was employed to quantify probe targets under competitive conditions against parent inhibitors, and in a DNA damage response model. An alternative to using literature inhibitors is to derive novel starting points for tool design through a fragment-based drug discovery approach. A high throughput screen against the minimal catalytic core of HOIP, an E3 ligase, is described together with subsequent validation and characterisation of hit fragments by waterLOGSY NMR and Micro-scale thermophoresis, and crystallography attempts. Finally, a model system for the structural analysis of transient enzyme complexes is explored, to further our understanding of these interactions and ultimately to assess the applicability of these complexes for future drug discovery. The design and synthesis of a maleimide trap is described, along with its application to covalently trap an Ub-E2-E3 complex.

This thesis is a 'descriptive analysis' of drug use and drug selling as it occurred in different leisure venues and settings and among different audiences participating in the London rave dance culture. It is an ethnographic study informed through a 'participant observer' approach. The main methods used were field observations carried out in nightclubs and dance parties and through informal interviews with people attached to different rave dance social networks. The central objective of the study was to examine the ways in which drug selling was organized and the social processes that underpinned drug transactions. Theoretical and conceptual constructs located within the discipline of urban sociology are drawn upon. A reflexive engagement with the ethnographic process and the ethical dilemmas encountered in undertaking a study of illegal activity is provided. The data is analysed using a macro and micro organizational framework. Broadly, drug selling is differentiated by trade in public spaces for instance in nightclubs and dance parties; and in private spaces in houses where transactions were based primarily among friendship group acquaintances. The camaraderie among rave dance participants greatly assisted drug sales and the expansive nature of friendship groups meant drug selling operations easily developed beyond that initially intended. The central themes underpinning the empirical analysis focus on notions of entrepreneurialism and enterprise. It is argued that rave dance participants were economic actors involved in the production of the culture and economy of which they were a part. A related concept is the way drug selling set-ups could function as 'alternate work' and meaningful activity. A central concept underpinning this thesis is the notion of contemporary youth sociality and shifting identities. The 'fluid' forms of socializing observed in my study in respect to drug cultural involvement, mirrored the notion that in late-modern society youth socializing is about moving from one group to another depending on how one chooses to express and shape their self-identity. The conclusion of the thesis argues that, this freedom to attach oneself to different social worlds was more of an option for people from advantaged social class backgrounds, than it was for those from less privileged backgrounds.

This study traces the development of forensic medicine, forensic science and police science from their roots in nineteenth-century England and shows that the main factors which make up the present-day disciplines were in place well before the First World War. The elite practice of forensic medicine had evolved into the laboratory-based sciences of special pathology and Home Office toxicological analysis by the 1900s and it is shown that in creating forensic science in the 1930s on this elite medical model as an aid to police investigations, other science and medicine in court, particularly in the civil courts, were excluded from the meaning of the new term 'forensic science' and perhaps also from the far older and wider 'forensic medicine'. There is confusion in the public mind as to the difference between forensic medicine and forensic science, or whether one is included in the other. By outlining the history of the separate specialities the meanings of the terms is clarified, not only for the present day, but at each earlier stage. Forensic medicine's role working for the state in criminal cases has always been badly funded, as the discipline has been unable to compete for public funds against more pressing needs. poor teaching and little or no original research. The creation of the Forensic Science Service was an attempt in part to salvage forensic medicine and to put it finally on an institutionalised footing, but this failed, and as the period of review closed in 1946 forensic medicine was still struggling for survival. Forensic science too looked set for failure as the government had made no provision for research or for training the new 'forensic scientists'.

Throughout the early Middle Ages, the Clare earls of Hertford and. Gloucester were prominent figures on the political scene. Their position as baronial leaders was derived from their landed wealth, and was built up gradually over two hundred and fifty years. Richard I de Clare arrived in England in 1066 as a Norman adventurer, and was granted the honours of Tonbridge and Clare. The family more than doubled its lands during the twelfth and thirteenth centuries, mainly by inheritance, the greatest acquisition being the honour of Gloucester in 1217. Only in the first half of the twelfth century was the honour an autonomous unit. In the honour of Clare, the earls relied on their own tenants as officials in the twelfth century, but in the thirteenth the administration was professional and bureaucratic. The earl's relations with his sub-tenants are unknown before the early fourteenth century; then, in contrast to other estates, the Clare honour-court was busy, strong and fairly efficient. In contrast to the honours of Clare and Gloucester, held of the king in chief, Tonbridge was held of the archbishop of Canterbury, and the relationship between archbishop and earl was the subject of several disputes. As to franchises, the earl exercised the highest which he possessed in England at Tonbridge; elsewhere he appropriated franchises on a large scale during the Barons' Wars of 1258-1265, but most of these were surrendered as a result of Edward I's quo warranto proceedings In the thirteenth century, the Clare earls of Gloucester were important Marcher lords. They strengthened their authority in Glamorgan by expelling most of the Welsh princes in northern Glamorgan, and they long avoided royal interference in their liberties. Nevertheless, in the notorious case of the earls of Hereford and Gloucester in 1291-2, Edward I temporarily succeeded in breaking down March custom.

Refugees have resettled in the U.S. for decades and welcoming communities are charged with providing services to culturally and linguistically diverse groups of people. Women from Sub-Saharan Africa (SSA) have increasingly been resettled in the past decade and present specific challenges and opportunities to the health care system that serves them during pregnancy care. Pregnancy care in particular and maternal health care in general are of particular interest because they include services that have the potential to impact long-term health outcomes of families and because they are often a point of entry into the health care system. Through three studies, this dissertation examined the interactions between refugee women from SSA and their health providers in the context of maternity care through bioecological, socio-ecological, intersectional, and cultural competence theoretical frameworks. The first study used the PRISMA framework to systematically review what is known about the needs of women from SSA as they encounter the maternal health care system in the U.S. Results indicated that needs can be categorized as Clinical, Systemic, and Personal and recognized Strengths and Protective Factors. The second study is an in-depth case study that used interviews and observations to understand the experiences and perceptions of care received by two refugee women from the Democratic Republic of the Congo that were resettled in the southeastern U.S. Participants had different experiences of pregnancy care and these were related to the differences in personal characteristics between the participants. Personal characteristics influenced the participants’ ability to access care and their subsequent experiences and perceptions of that care. The third study used key informant interviews with medical doctors, nurse practitioners, and nurse midwives to understand their perceptions of the needs of refugee patients from SSA and their needs as health providers interacting within their respective clinics and the larger U.S. health system. Together, the studies elucidate the importance of culture as a factor in health care interactions and opportunities for service providers and public health professionals to bolster services in a way that allows for more seamless service delivery in a culturally competent manner that ultimately improves health outcomes and reduces health disparities.

The present study examined self-monitoring of blood glucose (SMBG) as part of a selfregulatory process of health decision-making using the Self-Regulation Model of illness perceptions, or Common Sense Model. Participants were N=185 individuals with type 2 diabetes from a specialty diabetes clinic prescribed subcutaneous insulin or other injectable diabetes medication at least daily. Collected information included both medical chart data and self-report questionnaires completed prior receiving lab results. Self-care burden was generally high; the modal prescribed times per day of injecting insulin was 4 with modal SMBG recommendations of 3-4 times per day. Participants reported high adherence to prescribed medication regimens, varied aherence to diet recommednations, and low engagement in exercise. Specific hypotheses were developed to examine the relationship between illness coherence and illness control beliefs (IPQ), SMBG decisionmaking behavior, and outcomes including diabetes distress (PAID) and hemoglobin A1c level. These hypotheses were not supported. Supplemental analyses revealed that SMBG decision-making use was related to illness perceptions, including a positive relationship with personal control and coherence beliefs, but not treatment control, and a negative relationship with both outcome variables (A1c at baseline and PAID score). Both treatment and personal control beliefs were not associated with glucose control outcomes, suggesting that illness beliefs alone do not explain why some individuals are more successful at managing their diabetes than others. Coherence was found to differ by education level and SES and greatly vary in an otherwise relatively homogenous sample. Study findings suggest that illness perceptions play an important role in the process of SMBG use for decision-making as it relates to glucose control and diabetes distress. Results also point to possible clinical targets such as illness coherence and diabetes distress. The study provides a foundation for future research related to SMBG as a decision-making strategy.

This study attempted to identify factors in seventh grade academics that are associated with overall success in tenth grade biology. The study addressed the following research questions: Are there significant differences in performance levels in seventh grade Criterion Referenced Competency Test (CRCT) scores in science, math, reading, and language arts associated with performance categories in tenth grade biology End of Course Test (EOCT) and the following demographic variables : gender, ethnicity, socioeconomic status, disability category, and English language proficiency level? Is there a relationship among the categorical variables on the tenth grade biology EOCT and the same five demographic variables? Retrospective causal comparative re search was used on a representative sample from the middle schools in three North Georgia counties who took the four CRCTs in the 2006-2007 school year, and took the biology EOCT in the 2009-2010 school year. Chi square was used to determine the relationships of the various demographic variables on three biology EOCT performance categories. Two- way ANOVA determined relationships between the seventh grade CRCT scores of students in the various demographic groups and their performance levels on the biology EOCT. Students’ performance levels on the biology EOCT matched their performance levels on the seventh grade CRCTs consistently. Females performed better than males on all seventh grade CRCTs. Black and Hispanic students did worse than White and Asian/Asian Indian students on the math CRCT. Students living in poverty did worse on reading and language arts CRCTs than students who were better off. Special education students did worse on science, reading, and language arts CRCTs than students not receiving special education services. English language learners did worse than native English speakers on all seventh grade CRCTs. These findings suggest that remedial measures may be taken in the seventh grade that could impact performance levels on the biology EOCT.